OBJECTIVES/GOALS: Illuminate processes and findings of the Environmental Scan of Adaptive Capacity and Preparedness of CTSAs done by the CTSA Working Group. Share challenges, strategies, and lessons learned for CTSAs to build Capacity to address clinical and translational barriers while responding to emergencies. METHODS/STUDY POPULATION: An Environmental Scan approach for searching, collecting, analyzing and using information from diverse sources regarding CTSA hubs experiences during emergency as related to research implementation, translation, support, adaptation, and preparedness: - Triangulating multiple data sources and mixed methods (e.g., literature review, document/RPPR analysis, and expert review); - Secondary analysis of the JCTS COVID-19 Survey of the CTSAs: challenges, lessons learned, and practices that work in various program components/areas; - Using feedback of CTSA professionals from multiple disciplines to enhance our knowledge of emergency preparedness and efficient adaptation to public health and other crises. RESULTS/ANTICIPATED RESULTS: The E-scan approach helped identify challenges, successful practices, and evidence-based strategies for building adaptive capacity and preparedness of CTSAs across various scientific sectors of the translational science spectrum. Some of the findings include: - Roadmaps for the creation of new collaborative research resources (biobanks; data repositories, etc.); - Rapid clinical and research decision making during public health crises; - New community-based research strategies to facilitate communication, research dissemination, and participant recruitment based on existing trust-based networks; - Innovative resource allocation to guarantee continuity of training and research opportunities for trainees. DISCUSSION/SIGNIFICANCE: The Environmental Scan of the Adaptive Capacity of CTSA hubs provides useful knowledge and tools to diverse clinical research stakeholders for mitigating the impact of a disaster via adjusting programs, practices, and processes, and building capacity for effective, emergency-ready and responsive research, training, and community engagement.

OBJECTIVES/SPECIFIC AIMS: The foci of this evaluation is to:. determine if cultural and contextual adaptations identified by community stakeholders via ShARP sessions change research design/implementation/dissemination strategies. examine changes in stakeholder engagement by the research team after the initial ShARP session. METHODS/STUDY POPULATION: CCH staff measured session effectiveness for multiple stakeholders at multiple time points. Researchers and community stakeholders completed surveys to assess process and function at the end of the session. CCH staff follow-up with researcher team members approximately 12-18 months after the session to assess longer term outcomes and changes resulting from stakeholder input gathered at the ShARP. RESULTS/ANTICIPATED RESULTS:. 16 ShARPs sessions were hosted in a three year period. o 4 hosted in Spanish o 2 focused solely on youth populations. 141 stakeholders representing diverse professional backgrounds participated in sessions and represented a cross section of: o Ages: 12- 17 (5%); 18-24 (6%); 25-34 (24%); 35-44 (23%); 45-54 (12%); 55-64 (9%); 65 and older (13%); No Response (8%) o Gender Identities: Female (62%); Male (34%); Transgender (0%); No Response (4%) o Race/Ethnicities: Asian, Pacific Islander (13%); African American/Black (28%); Hispanic/Latino/x (25%); Native Americans, First Nations, American Indian (0%); Caucasian/White (24%); Multiracial (2%); No Response (9%). Feedback from research teams (aggregate of Strongly Agreed/Agreed responses) o ShARP panel was made up of relevant stakeholders (97%) o ShARP session was worthwhile (100%) o Stakeholder input will improve my research project (100%) o I would engage stakeholders in future projects (40%). Feedback from community stakeholders (aggregate of Strongly Agreed/Agreed responses) o ShARP session worthwhile (89%) o I have an increased understanding of research after participating in this session (89%) o Based on the experience, would consider providing input on a research study in the future (90%) o This session was the first time I was asked to provide input on a research study (46%) DISCUSSION/SIGNIFICANCE OF IMPACT: Preliminary results indicate engaging stakeholders in research can provide cultural and contextual adaptations that increase research relevance and feasibility in any phase of research. Conversely, stakeholders indicated an increased understanding of research. This poster will feature stakeholder and researcher perspectives. Increasing dialogues between research teams and community stakeholders can improve research design and relevance. The ShARPs programs aims to increase these types of dialogues which can be especially important for research teams who are unsure of who or how to begin engaging stakeholders in research. Gathering additional data via follow-up interviews will help us better understand the impact this program has on long term stakeholder engagement in research.

Objectives/Goals: 1. Demonstrate the need to apply principles of community-engaged research to various stages of the research process. 2. Outline the process of using CE Studio(s) to redesign an interview guide for service providers of youth involved in the justice system. Methods/Study Population: Service-providers provide a critical lens with which to view the sexual health needs of justice-involved youth. Minimal research describes the unique perspectives of those who work directly with this vulnerable population to address their sexual health needs. The goal of this project is to outline the process of using CE Studio(s) to redesign an interview guide for service providers. The guide is aimed at gathering insight into the knowledge, access, and use of sexual health services for justice-involved youth. Preparation involves the preplanning phase, including the drafting of the interview guide; engagement consists of recruitment and implementation of the CE Studio; and restructuring will outline the application of feedback and finalization of the interview guide. Results/Anticipated Results: During the preparation phase, the researcher was tasked with (1) developing a visual guide to highlight key points of the research study and (2) providing a draft of the tentative interview guide for review prior to the CE Studio session. For the engagement stage, participants were recruited from listservs, community organizations, and word-of-mouth to participate in a session facilitated by a member of the CE Studio team. Lastly, we anticipate that the restructuring phase will not only allow us to use feedback from the CE Studio session to alter the interview guide but provide insight into potential recruitment strategies for the overarching research project. Discussion/Significance of Impact: Leveraging CE Studios to elicit feedback from service providers will provide unique insight into addressing the sexual health needs of justice-involved youth. We expect that the overall CE Studio process and feedback will be integral in eliciting strong qualitative feedback and shaping the implementation of the overall research project.

Objectives/Goals: Community engagement is required to translate scientific discovery into improvements in health. Lived experience is essential knowledge for translational research activities. Community studios facilitate interaction between researchers and community members, but mechanisms of how lived experience integrates into research are under explored. Methods/Study Population: The community studio program at the Center for Community Health Partnership and Research was evaluated through interviews with participating community health consultants (CHCs) and researchers. Fifteen facilitated community studios held since 2023 were included. Study participation was organized by studio: invitations went to all researchers, and then to three CHCs randomly selected from each researcher’s studio. Rapid qualitative analysis methods were used to create analysis templates based on key questions from the interview guide. Interview notes were summarized according to the template and compiled into matrices for study team reflection and discussion. Responses to key questions were articulated during group discussions and iteratively refined. Results/Anticipated Results: Thirteen researchers and 25 CHCs were interviewed from April to June 2025. Eighty-six percent of researchers had a research degree, either a PhD or Master’s; 85% were associate or full professors. None reported formal training in community engaged research. Several types of knowledge gaps were filled including correction of faulty assumptions, awareness of the impacts of SDOH, and ideas for solving operational challenges. CHCs were 80% female. CHCs felt valued during the studio experience, received benefit from hearing the lived experiences of others, and gained new perspectives on their health issue. CHCs expressed a desire to know the impact their participation had on the research, and several said they would have to see it to believe it. Both researchers and CHCs appreciated the expert facilitator. Discussion/Significance of Impact: Everyone learned during studios. Eliciting lived experience filled different knowledge gaps. Sharing provided social benefits and studios functioned like a third space, a merging between the built and social environment. An expert facilitator played key roles that included fostering belonging and translation of lived experience into knowledge.

Fair inclusion of research subjects is necessary to ensure that post-acute sequelae COVID-19 (PASC) research results benefit all members of society. Scientists should conduct research on a broad sample of individuals who represent clinically relevant factors influencing a disease. Without demographic diversity and sociological and environmental variability, research outputs are less likely to apply to different populations and would thus increase health disparities. The goal of this narrative literature review and ethical analysis is to apply fair selection criteria to PASC research studies. We briefly highlight the importance of fair subject selection in translational research and then identify features of PASC, as well as PASC research, that hinder fair inclusion of research participants. We will demonstrate that determining an adequate and representative sample is not simply a matter of ensuring greater diversity; rather, fairness requires a broader evaluation of risks, burdens, and benefits specific to underrepresented populations. We provide recommendations to ensure fair subject selection in PASC research and promote translation toward positive health outcomes for all individuals, including the most vulnerable.

Objectives/Goals: Cross-institutional collaboration describes the development of cross-institutional partnership between two CTSI’s to overcome common challenges faced by both entities. Community engagement work discusses ways that Strategic Doing fostered sustainable initiatives to improve wellness in rural communities. Methods/Study Population: Through collaborative efforts, the Indiana and Penn State University Clinical & Translational Science Institutes were able to plan and implement community engagement initiatives to advance health outcomes among under-resourced populations in each of their respective communities. The institutions shared and utilized key principles of an educational series entitled “Strategic Doing (SD)” that provided instruction on developing and facilitating complex collaborations. Leveraging SD practices, both CTSI’s community engagement teams guided groups of local community leaders and stakeholders in meaningful, action-oriented partnerships to promote better health and wellness. Results/Anticipated Results: At Indiana CTSI, six staff completed Strategic Doing Institute Agile Leadership training. As a result, community partners in 11 counties implemented evidence-based strategies, including a community garden with cooking classes, a mobile kitchen for nutrition education, and wellness passports at community events with food samples, screenings, and educational programs. At Penn State, twelve staff (9 CTSI, 3 community partners) completed the same training. Of 8 post training evaluation respondents, 75% were extremely likely and 25% somewhat likely to apply the training to their work. Trainees are leading task forces that received CTSI funding focused on substance use, healthy aging, and public health infrastructure and health literacy. Discussion/Significance of Impact: SD trainees have reported transformative changes when facilitating community-academic partnerships. By using a scientifically based framework, task forces have experienced enhanced synergy, resulting in increased engagement and accountability that led to improved wellness in the community.

OBJECTIVES/GOALS: Target: Computationally identify the markers of ulcer severity and risk of amputation from datasets that include demographics data, clinical, laboratory data, and medical history over 6000 patients. METHODS/STUDY POPULATION: In this study we will use tables of demographics such as age, gender, and ethnicity/race. Inspired by previous research we’ll include wound age (duration in days), wound size, number of concurrent wounds of any etiology, evidence of bioburden/infection, Wagner grade, being non ambulatory, renal dialysis, renal transplant, peripheral vascular disease, and patient hospitalization. Another table will include laboratory vital signs to include physiological variables such as height, weight, body mass index, pulse rate, blood pressure, respiratory rate, and temperature. We’ll include also social data like smoking status, socio-economic status, housing condition. RESULTS/ANTICIPATED RESULTS: Our project aligns with previous efforts to identify high risk Diabetic Foot Ulcer individuals but also takes a different perspective by collecting and marking clinical data from a subset of patients (e.g., severity, Hispanic versus non-Hispanic) and computationally process these data to provide a tool that can identify DFU severity and high-risk patients. We will obtain samples from Hispanics and non-Hispanics because these two groups are likely to have significant differences in the progression of ulcer severity. The rationale is that by comparing these two groups, we will assess and study the factors that are differentially present. It is our expectation that the proposed project will provide an easy-to-use tool for DFU progression and risk of amputation and contribute to identify high-risk individuals. DISCUSSION/SIGNIFICANCE: Diabetes prevalence estimates in Bexar County, TX exceeds national estimates (15.5% vs. 11.3%) and diagnosed cases are higher among Hispanic adults (13.4%) compared to their non-Hispanic white counterparts (9.5%). Late identification of severe foot ulcers minimizes the likelihood of reducing amputation risk.

Objectives/Goals: Despite significant advancements, adolescent and young adult (AYA) patients with hematologic malignancies continue to have inferior improvement in survival over time compared to their younger and older peers. This project assesses which patient and neighborhood characteristics are associated with clinical trial enrollment in this population. Methods/Study Population: We will perform a retrospective study of individuals, aged 15–39, diagnosed and treated at Children’s Healthcare of Atlanta (CHOA) or Winship Cancer Institute for hematologic malignancies between 2011 and 2023. Our primary exposure variables will be race/ethnicity, the area deprivation index (ADI), and the index of concentration at the extremes (ICE). The primary study outcome will be enrollment in an open frontline therapeutic clinical trial (yes vs. no). Our analyses will estimate the crude and adjusted odds ratio of clinical trial enrollment according to race/ethnicity, ADI, and ICE; these analyses will be adjusted for co-variables of interest (e.g. patient primary language, and insurance provider). As a secondary analysis, we will further subdivide the patients by treatment location and by age tertiles. Results/Anticipated Results: Our study team completed preliminary work looking at institutional clinical trial enrollment in a pediatric-only (Discussion/Significance of Impact: We expect that this study conducted in a large, diverse AYA cohort will reveal key associations about likelihood of clinical trial enrollment. Once these associations are known, we can develop and test interventions –such as augmented social work involvement and assistance with transportation– to mitigate the effect of amenable risk factors.

Objectives/Goals: The growing burden of hypertension in the USA disproportionately impacts individuals with lower socioeconomic status and those in rural communities. This study aims to investigate specific social determinants of health associated with uncontrolled hypertension among rural, underserved patients residing in Alabama. Methods/Study Population: A retrospective review of electronic health records data from the UAB Selma Family Medicine clinic was conducted. The deidentified data were entered into the Population Health Assessment Engine (PHATE) to render social characteristics and community vital sign (CVS) scores, a social deprivation index, by census tracts. We provide descriptive statistics and compare the stated factors between patients with controlled and uncontrolled hypertension using logistic regression models. We are conducting phone surveys to gather individualized data on social determinants of health to assess the perceived social needs of patients with hypertension. The Protocol for Responding to & Assessing Patients’ Assets, Risks & Experience tool was used to develop the survey, and survey responses will be compared with the PHATE results. Results/Anticipated Results: Among 2129 patients, 375 (17.6%) had uncontrolled hypertension with a mean age of 58.7 ± 14.4 years. Women comprised 66.7% (250) and 65.1% (1142) of the uncontrolled and controlled hypertension populations, respectively. The prevalence of uncontrolled hypertension was 19.1% among Black patients and 8.2% in White patients. Patients with uncontrolled hypertension had a CVS of 82.37 ± 7.31 and 81.81 ± 8.40 patients with controlled hypertension. Patients with uncontrolled hypertension lived in areas where an average of 46 ± 11% were not employed, 36 ± 9% rented, and 28 ± 1% lived below the federal poverty line (FPL). Adjusting for age, race, and sex, a unit increase in the proportion of people below the FPL was associated with 43% higher odds of uncontrolled versus controlled hypertension (OR  =  1.43, 95% CI 0.44, 4.64). Discussion/Significance of Impact: Rural, underserved patients with hypertension experience multiple adverse social determinants, such as nonemployment rates, low income, and rental housing. Survey results will allow us to compare assessed and individualized social determinants that may be important to address when caring for this population.

OBJECTIVES/GOALS: Cardiovascular disease (CVD) is the most common cause of death in systemic lupus erythematosus (SLE). Genome-wide association studies have identified single nucleotide polymorphisms linked with CVD risk, but the association with SLE is not well established. We aimed to determine associations using machine learning in a multi-ethnic lupus cohort. METHODS/STUDY POPULATION: We will use data from the established SLE cohort study named Genetic Profile Predicting the Phenotype (PROFILE). PROFILE was constituted in 1998 by combining existing cohorts at multiple sites which are also of defined ethnicity (Hispanics of Mexican ancestry and Puerto Rico, African American, and Caucasian). The cohort consists of 3,118 individuals and the database contains socioeconomic–demographic, clinical, laboratory, and genetic variables. Genetic data consist of 196,524 single nucleotide polymorphisms. To detect risk genes and predict an individual’s SLE risk will design a random forest classifier using SNP genotype data. Logistic regression models will be performed with CVD as the outcome, adjusted for age, sex, ethnicity, disease duration, and traditional and nontraditional risk factors for CVD. RESULTS/ANTICIPATED RESULTS: We expect to find several established and new susceptibility genes associated with CVD. DISCUSSION/SIGNIFICANCE: This approach offers an opportunity to characterize distinct genetic risk factors and the relationship of CVD with SLE. These data may be important in the identification of patients at high risk for such events and may allow the design of preventive strategies which may beneficially have an impact on the morbidity and mortality of SLE patients.

OBJECTIVES/GOALS: Our goal is to determine whether microplastic fibers (MPFs) provide signals for dendritic cell-induced Th2 polarization via epithelial-cell-derived thymic stromal lymphopoietin (TSLP). We seek to highlight a potential mechanism for MPF-induced airway toxicity associated with asthma exacerbation. METHODS/STUDY POPULATION: Primary human bronchial epithelial cells (NHBEs) were grown and differentiated at an air-liquid interface. Dyed and undyed polyester MPFs (14x45 µm) generated using a cryomicrotome were delivered to NHBEs through a custom designed mesh-hopper system. After the exposure period (6, 12, 24 hrs), cell viability was assessed using alamarBlue, and RT-qPCR was performed to determine mRNA expression of asthma associated genes (i.e., TSLP, IL-13, IL-33, etc.,) in NHBEs. Bulk mRNA-sequencing followed by bioinformatics will be performed to observe other plausible pathways tweaked by lung cell exposure to MPFs. RESULTS/ANTICIPATED RESULTS: Through gravimetric analysis, it was determined that the mesh-hopper system can achieve delivery efficiencies of at least 85% for as low as 500 fibers. Following exposure, results show polyester MPFs (500 - 1,000 fibers) exposed to NHBEs at multiple time points (6, 12, 24 hrs) did not result in a statistically significant decrease in cell viability. Treatment with 500 undyed MPFs resulted in a slight increase in TSLP expression at 6 hrs that decreased over time, whereas all other treatment groups resulted in TSLP downregulation. Similarly, 500 undyed MPFs resulted in an increase in IL-13 expression at both 6 and 12 hrs with all other treatment groups leading to IL-13 downregulation. We anticipate the RNA-seq results will show pro-inflammatory pathways are highly targeted following NHBE exposure to MPFs. DISCUSSION/SIGNIFICANCE: This study is one of the first to mechanistically assess the impact of MPFs on lung cells while simultaneously addressing the need for a reliable system that delivers MPFs to ALI cultures to better mimic inhalation and avoid inadequate resuspension of particles in liquid medium.

OBJECTIVES/GOALS: To demonstrate safety and limit damage to off-target organs, we will be determining dosimetry parameters through experimentation and Monte Carlo simulations with our brachy therapy applicator designed to improve upon current designs to treat a 3-dimensional volume. METHODS/STUDY POPULATION: Low-cost materials were used to manufacture our High Dose Rate (HDR) applicator and a readily available after loading system was used to load our configuration with a radioactive source. The dosimetry of our device was analyzed using commercially available software and external beam therapy films to generate depth dose profiles and superficial dose distribution. Additionally, we attempt to confirm Task Group No. 43 (TG-43) dosimetry parameters using Monte Carlo simulations for our device. These data were compared with currently available applicators used for intraoperative radiotherapy. RESULTS/ANTICIPATED RESULTS: We anticipate that we will be able to validate dosimetry parameters for our device in preparation for clinical use. We aim to show our dose distributions align well with proposed target volumes while considering the composition and shape of our applicator. We hope to demonstrate that, unlike current applicators, our design is more effective at treating a 3-dimensional target volume. DISCUSSION/SIGNIFICANCE: By 2040, pancreatic cancer will be the second-largest cause of cancer-related deaths. Even with current brachytherapy applicators, 30-40% of pancreatic cancer seems to recur near the surgical site after surgery. By preventing local recurrence, we hope to improve patient outcomes.

OBJECTIVES/GOALS: Strip craniectomy with orthotic helmet therapy (SCOT) and open cranial vault reconstruction (OCVR) are mainstay surgical treatments for sagittal craniosynostosis. The purpose of this study is to compare long-term morphologic outcomes of the skull, subjective appearance, and perioperative outcomes between patients who underwent SCOT and OCVR. METHODS/STUDY POPULATION: Patients who underwent SCOT or OCVR for isolated, non-syndromic sagittal craniosynostosis with preoperative computerized tomography (CT) imaging were identified at UCSF between 2000 and 2020. Perioperative outcomes were extracted from the medical chart. Anthropometric measurements will be used to assess baseline severity using preoperative CT imaging and postoperative skull morphology using 3D camera imaging. Patient satisfaction surveys will be administered to parents at the time of postoperative 3D imaging. Subjective appearance will be rated among adolescents and craniofacial surgeons using patients’ postoperative 3D imaging. Descriptive statistics will be calculated using Student’s t test and Mann-Whitney U. Chi-square tests and Fisher exact tests will be used to compare categorical outcomes. RESULTS/ANTICIPATED RESULTS: 47 patients were included in the study (18 SCOT and 29 OCVR) with similar follow-up between groups (SCOT 2.3 +/- 1.5, OCVR 2.6 +/- 2.0). There were no significant differences in sex or race. OCVR had longer operative times (p-value 0.0003), higher estimated blood loss (p DISCUSSION/SIGNIFICANCE: SCOT was associated with superior perioperative outcomes compared with OCVR due to its minimally invasive technique. Our results for long-term healing outcomes and subjective appearance may further guide craniofacial surgeons in selecting the most optimal operative technique.

OBJECTIVES/GOALS: This study seeks to culture and characterize mucus-degrading microbes from the microbiome of inflammatory bowel disease (IBD) patients. METHODS/STUDY POPULATION: Stool will be collected from IBD patients and healthy first-degree relatives, then enriched for mucin-degrading microbes through growth on porcine rectal mucin. Dilution plating in both liquid and solid culture formats will be employed to isolate strains capable of growth on mucin. Cultures that are positive for mucin degradation will be identified with 16S rRNA sequencing; unique isolates will be genome sequenced and transcriptionally profiled on simple monosaccharides and mucin in order to identify putative mucin-degrading genes. The abundance of novel enzymes, pathways, and microbes will be compared in healthy and IBD patient populations using existing datasets in the literature. RESULTS/ANTICIPATED RESULTS: We expect to isolate previously uncultured mucin-degrading microbes, which will likely include new strains and possibly new species of bacteria. Through the transcriptomic characterization of mucin-degrading pathways, we will expand the lexicon of known mucin-degrading enzymes and pathways used by bacteria in the human colon. We expect mucin-degrading microbes to be more abundant and active in IBD patients compared to healthy controls. DISCUSSION/SIGNIFICANCE OF IMPACT: There is no cure for IBD and treatment relies heavily on suppressing a patient’s immune system. This research seeks to understand the contribution of the gut microbiota in the pathogenesis of IBD, which may lead to future therapeutic targets.

ABSTRACT IMPACT: This work describes, for the first time, the methylome in patients with T-LGLL, focusing on the IL-15 promoter, and clearly demonstrates that 5-azacytidine decreases IL-15 production leading to T-LGLL cell death. These results form the basis a translational clinical trial in T-LGLL that will begin accrual in 2021 OBJECTIVES/GOALS: T-LGLL is an incurable leukemia with few treatment options driven by overexpression of IL-15. Our objective is to characterize the methylation status of the IL-15 promoter in T-LGLL patients and evaluate the potential use of 5-azacytidine (5-aza) in a translational trial by studying the effect of 5-aza in vitro on IL-15 levels, and the IL-15 promoter. METHODS/STUDY POPULATION: We sorted T-LGLL patient (n=3) and normal donor (ND) samples (n=3) for CD3+/CD8+/CD5-/dim for T-LGLL immunophenotype. We analyzed DNA methylation and gene expression profiling using reduced representation bisulfite and RNA sequencing and determined differential methylation and gene expression using 1-way ANOVA analysis. To determine the functional significance of differential methylation, we evaluated MOTN-1 T-LGLL cell viability in vitro with 5-aza at increasing concentrations. Next, we evaluated IL-15 gene expression in MOTN-1 cells treated with 5-Aza versus MOTN-1 with control using western immunoblot. Finally, we exposed MOTN-1 cells to a novel IL-15 inhibitor, IBI-15, and compared cell viability against MOTN-1 cells exposed to an inactive control. RESULTS/ANTICIPATED RESULTS: There was significant differential methylation (P= 0.0178) and expression (P =0.0059) in T-LGLL patients vs ND. These data revealed significant differential hypermethylation of gene promoters, including an increase in DNA methylation of the IL-15 promoter in T-LGLL cells vs ND. In MOTN-1 cells treated in vitro with 5-Aza at 24 and 48 hours, a dose-dependent decrease in the viability of T-LGLL cells was observed, from 100% to 49.5%, p=0.037. Further, a marked decrease in IL-15 expression was observed at all concentrations of 5-aza compared to control (p=0.0001). Finally, a decrease in cell viability was observed utilizing the IL-15 inhibitor IBI-15 vs control. These results confirm that 5-aza leads to decreased transcription of the IL-15 gene, possibly due to hypomethylation of the IL-15 promoter. DISCUSSION/SIGNIFICANCE OF FINDINGS: Hypermethylation of the IL-15 promoter and subsequent increase in IL-15 is critical to the pathogenesis of T-LGLL. Inhibition of the IL-15 promoter by 5-aza leads to down-regulation of the IL-15 gene transcript, which is sufficient to induce T-LGLL cell death. Based on these results, a phase I trial will be conducted using CC-486 (oral 5-Aza) in T-LGLL.